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Biomedical subjects

P A Singer

Publications and source records attributed to P A Singer.

At least 127 records · Page 7Linked to original sources
PubMed1990

Coding sequence polymorphisms among V beta T cell receptor genes.

The four V beta gene segments, V beta 1, 3.1, 6, and 10, which previously have been shown by RFLP analyses to differ between TCR V beta a and V beta b haplotypes, were cloned and sequenced from V beta a SWR mice and compared with V beta b strains to define coding sequence polymorphisms distinguishing these haplotypes. V beta 3.1 and 6 alleles differed between strains by a single amino acid, whereas V beta 1 and 10 alleles differed by 4 and 6 amino acids, respectively. The overall interhaplotypic V beta polymorphisms appeared to be limited when based upon compilation of this information and previously published V beta sequences. One application of these data was to attempt to elucidate the molecular basis underlying the recently reported allele-specific autoimmune disease, collagen-induced arthritis. Based on the present structural data and the additional evidence, contrary to what was suggested, the V beta 6 gene does not appear to be the sole participant in anticollagen responses.

Amino Acid Sequence↗
PubMed1990

Thymic selection defines multiple T cell receptor V beta 'repertoire phenotypes' at the CD4/CD8 subset level.

We describe here the use of a sensitive and accurate multiprobe V beta RNase protection assay in characterizing the expression levels of 17 V beta genes in separated CD4+ and CD8+ subsets of selected mouse strains. The IE-reactive V beta genes (V beta s 11, 12, 5.1 and 16) showed various patterns of skewed subset expression in different strains, suggesting additional influences of IA, class I, and non-MHC genes in the selection process. Clonal deletion of V beta 11- and V beta 12-bearing T cells, among others, was skewed strongly towards the CD4+ subset in many IE+ mouse strains, supporting the notion that negative selection can cause incomplete, subset biased, V beta clonal deletions. Broad analysis in separated CD4+ and CD8+ subsets gave improved resolution of V beta repertoire selection, and revealed significant strain and/or subset specific skewing for additional V beta genes; with consistent bias towards higher expression of V beta 7 and V beta 13 in the CD8+ subset, and V beta 15 in the CD4+ subset of most mouse strains. The influence of diverse non-MHC ligands in V beta repertoire selection was further illustrated by the identification of unique V beta repertoires for six different MHC-identical (H2k) strains. Such polymorphisms in TCR repertoire expression may help to define better disease susceptibility phenotypes.

Animals↗
PubMed1990

Central changes in hypothyroid myopathy: a case report.

A muscle biopsy from a patient with hypothyroid myopathy showed striking central changes. "Cores" were seen in most type 1 fibers with oxidative enzyme preparations. Electron microscopy of these areas revealed Z disc streaming, myofilament disruption, and absent mitochondria. The myopathy rapidly improved with thyroxine treatment. This biopsy is of interest, as numerous "cores" have not previously been reported in hypothyroid myopathy.

Humans↗
PubMed1990

The ethical assessment of innovative therapies: liver transplantation using living donors.

Liver transplantation is the treatment of choice for many forms of liver disease. Unfortunately, the scarcity of cadaveric donor livers limits the availability of this technique. To improve the availability of liver transplantation, surgeons have developed the capability of removing a portion of liver from a live donor and transplanting it into a recipient. A few liver transplants using living donors have been performed worldwide. Our purpose was to analyze the ethics of liver transplants using living donors and to propose guidelines for the procedure before it was introduced in the United States. We used a process of "research ethics consultation" that involves a collaboration between clinical investigators and clinical ethicists. We concluded that it was ethically appropriate to perform liver transplantation using living donors in a small series of patients on a trial basis, and we published our ethical guidelines in a medical journal before the procedure was introduced. We recommend this prospective, public approach for the introduction of other innovative therapies in medicine and surgery.

Directed Tissue Donation↗
PubMed1990

Increased glucose use in the hypoglossal nucleus after hypoglossal nerve transection in aged rats.

We used [2-14C]deoxyglucose as a marker of increased metabolism of the hypoglossal nucleus after transection of its nerve. We studied this metabolism in 3-, 12-, and 24-month-old rats. We found an increase in glucose uptake in the control nucleus of 24-month-old rats which was significant when compared to that of 3-month-old rats. We also found a twofold increase in the difference between glucose uptake on the side of nerve transection compared to the control side in old rats.

Aging↗
PubMed1990

Novel origin of lpr and gld cells and possible implications in autoimmunity.

The lpr and gld mutations are prime examples of single-gene defects associated with expansion of a unique double-negative (CD4-8-), T-cell receptor alpha:beta + cell population and heightened polyclonal and autoimmune responses. The exact origin of these autoimmunity-inducing/enhancing T cells remains controversial. Here, we review the characteristics of the lpr and gld mutations, and speculate on the possible relationship of these cells to normal thymic differentiation pathways. We argue that mounting evidence now supports the existence of a CD4/CD8-loss pathway of late thymic differentiation, responsible for the origin of both normal and lpr/gld double-negative alpha:beta + cells. We further speculate that downregulation of CD4 and CD8 accessory molecules on thymocytes with moderately autoreactive T-cell receptors is involved in selecting cells, including lpr/gld precursors for this pathway. Escape of a large number of such autoreactive cells from thymic elimination might be an important contributory factor to the pathogenesis of autoimmunity.

Animals↗
PubMed1990

A review of public policies to procure and distribute kidneys for transplantation.

The purpose of this article is to provide an up-to-date review of the current status of frequently changing public policies for the procurement and distribution of donor kidneys for transplantation. Issues in procurement involve the Uniform Anatomical Gift Act, criteria for brain death, routine inquiry/required request policies, and the use of living kidney donors. Issues in distribution involve access to the transplant waiting list and use of the new national point system to select recipients from the list. These public policies are relevant for internists, who often care for potential organ donors and patients with end-stage renal disease. The issues are also relevant for policy-minded physicians because renal transplantation is the paradigm for organ transplant policy.

Disclosure↗
PubMed1989

Tolerance-related V beta clonal deletions in normal CD4-8-, TCR-alpha/beta + and abnormal lpr and gld cell populations.

We have analyzed tolerance-related clonal deletion of Mls-and I-E-reactive thymocytes at the RNA level using a multi-V beta probe RNAse protection assay, and used this phenomenon to identify the maturation stage of the abnormally expanded CD4-8-, TCR-alpha/beta + subset in lpr and gld homozygous mice, and of the phenotypically similar minor thymocyte subset found in normal mice. Essentially complete V beta clonal deletions were detected in lpr and gld cells of all appropriate background strains. Substantial, but not complete, V beta clonal deletions were also detected in the CD4-8- TCR-alpha/beta + subset of normal mice. Since expression of CD4/CD8 is required for V beta clonal deletions to occur, we conclude that lpr and gld cells, and at least a portion of CD4-8- TCR-alpha/beta + thymocytes in normal mice, are derived by secondary loss of CD4/CD8 accessory molecules from more mature CD4+8+ precursors. One possible interpretation of these findings is that such CD4/CD8 loss may affect a class of self-reactive thymocytes that have escaped direct clonal deletion. Exportation and expansion of such cells in the periphery may be an important contributory factor in the induction of systemic autoimmunity.

Animals↗
PubMed1989

Informed consent in emergency research. Prehospital thrombolytic therapy for acute myocardial infarction.

Can the conscious patient in the midst of a medical emergency provide adequate informed consent for a clinical research protocol? Adequate consent is crucial to the ethical conduct of clinical trials, including those performed in emergency settings. We examine the problem of emergency informed consent. As an illustrative case, we discuss a pilot trial of prehospital thrombolytic therapy for myocardial infarction. Federal regulations for clinical research do not provide clear guidelines on emergency research in the conscious patient. Clinical investigators currently approach emergency consent in four ways: (1) avoid such research, (2) omit the consent process, (3) obtain deferred consent, or (4) obtain customary consent. We suggest a fifth alternative, two-step consent, which permits the conduct of emergency research while protecting the rights of the emergency research subjects. Such a process may serve as an alternative solution for future studies faced with the problem of informed consent in emergencies.

Emergencies↗